Squamous Cell Lung Cancer: Review of Biochemical Aspects, Cellular Signals, and Pharmacological Treatments | ||||
| Egyptian Journal of Chemistry | ||||
| Articles in Press, Accepted Manuscript, Available Online from 05 September 2025 | ||||
| Document Type: Review Articles | ||||
| DOI: 10.21608/ejchem.2025.400356.11995 | ||||
 View on SCiNiTO | ||||
| Author | ||||
Sultan Suleiman Issa Al-Harb 
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| Ministry of National Guard Health Affairs MNGHA, Saudi Arbia | ||||
| Abstract | ||||
| Background: Squamous cell carcinoma (SCC) of the lung is the second most common non-small cell lung cancer (NSCLC), strongly associated with smoking and central airway location. Despite declining incidence due to reduced smoking rates, it remains a major cause of cancer mortality, with unique histopathological and molecular features distinguishing it from other NSCLC subtypes. Aim: This review examines the biochemical pathways, cellular signaling, diagnostic approaches, and evolving treatment paradigms for SCC, emphasizing recent advances in immunotherapy and targeted therapy. Methods: A comprehensive analysis of peer-reviewed literature was conducted, focusing on SCC epidemiology, pathogenesis (particularly tobacco-induced carcinogenesis), diagnostic imaging/pathology criteria, and evidence-based treatment strategies across disease stages. Results: SCC accounts for ~30% of NSCLCs, characterized by keratin pearls/intercellular bridges on histology. Diagnosis relies on CT/PET imaging and immunohistochemistry (p40/p63 positivity). Treatment is stage-dependent: surgery for early-stage (IA-IIB), chemoradiation for locally advanced (IIIA-IIIB), and platinum-based chemotherapy ± immunotherapy (pembrolizumab/cemiplimab) for metastatic disease. PD-L1 expression ≥50% predicts immunotherapy response. Unlike adenocarcinoma, targetable mutations (EGFR/ALK) are rare (<5%), though emerging agents show promise for FGFR1/PIK3CA alterations. Conclusion: SCC management requires multidisciplinary integration of surgery, radiation, systemic therapy, and molecular profiling. Immunotherapy has improved survival in advanced disease, but limited targeted options underscore the need for biomarker discovery. Smoking cessation remains paramount for prevention. | ||||
| Keywords | ||||
| Squamous cell lung cancer; NSCLC; smoking-related cancer; PD-L1 immunotherapy; central lung tumors | ||||
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